Objective:To assess the efficiency and safety of combining lenvatinib with DEB-TACE for the treatment of unresectable large hepatocellular carcinoma,accompanied by PVTT,in order to provide insights into its potential as a therapeutic approach.Method:Patients with hepa-tocellular carcinoma and portal vein tumor thrombus,who were diagnosed and treated at Linyi Can-cer Hospital between June 2019 and June 2021,were chosen as the subjects of this study.Patient allocation into the experimental group(23 cases)and control group(27 cases)was based on indi-vidual preferences,ensuring a random distribution of participants.The DEB-TACE treatment was administered to the control group,while the experimental group received a combination of DEB-TACE and lenvatinib.The effectiveness of lenvatinib was assessed in the immediate post-surgery period,the patients'survival was monitored,and any associated side effects were documented.Result:3 months after treatment,the objective remission rates of the experimental group and the control group were 91.31％and 66.67％,and the disease control rates were 100％and 77.78％.The difference was statistically significant(P＜0.05).3 months after treatment,the regression rates of tumor thrombus in the experimental group and the control group were 60.87％and 29.63％,the difference was statistically significant(P＜0.05).The progression free survival time of the experi-mental group and the control group was 11 months and 8 months,the difference was statistically significant(P＜0.05);The median survival time of the experimental group and the control group was 20 months and 14 months,and the difference was statistically significant(P＜0.05).The main ad-verse reactions of the experimental group were hypertension,diarrhea,hand foot syndrome,rash,fatigue,loss of appetite,etc.,all of which were less than or equal to grade 3,and could be basically relieved after symptomatic treatment.Conclusion:The combination of DEB-TACE and lenvatinib is proven to be a safe and well-tolerated treatment for unresectable large hepatocellular carcinoma with portal vein tumor thrombus.This therapy not only effectively controls tumor progression but also prolongs survival time.

Objective To evaluate the in vitro effect of combinations of 5 β-lactam antibiotics with different β-lac-tamase inhibitors on the activity of multidrug-resistant Mycobacterium tuberculosis(MDR-TB),and identify the most effective combination of β-lactam antibiotics and β-lactamase inhibitors against MDR-TB.Methods MDR-TB strains collected in Henan Province Antimicrobial Resistance Surveillance Project in 2021 were selected.The mini-mum inhibitory concentrations(MIC)of 5 β-lactam antibiotics or combinations with different β-lactamase inhibitors on clinically isolated MDR-TB strains were measured by MIC detection method,and the blaC mutation of the strains was analyzed by polymerase chain reaction(PCR)and DNA sequencing.Results A total of 105 strains of MDR-TB were included in the analysis.MIC detection results showed that doripenem had the highest antibacterial activity against MDR-TB,with a MIC50 of 16 μg/mL.MIC values of most β-lactam antibiotics decreased significantly after combined with β-lactamase inhibitors.A total of 13.33％(n=14)strains had mutations in blaC gene,mainly 3 nu-cleotide substitution mutations,namely AGT333AGG,AAC638ACC and ATC786ATT.BlaC proteins Ser111 Arg and Asn213Thr enhanced the synergistic effect of clavulanic acid/sulbactam and meropenem on MDR-TB compared with synonymous single-nucleotide mutation.Conclusion The combination of doripenem and sulbactam has the strongest antibacterial activity against MDR-TB.Substitution mutations of BlaC protein Ser111 Arg and Asn213Thr enhances the sensitivity of MDR-TB to meropenem through the synergy with clavulanic acid/sulbactam.

Cerebroprotein hydrolysate oral liquid (COL) is a neuroprotective preparation composed of various amino acids and peptides, which has beneficial effects on diverse central system diseases. However, the therapeutic effect and potential mechanism of oral COL on ischemic stroke (IS) still need to be explored. This study aims to investigate the therapeutic effects and underlying mechanisms of COL on IS in vivo and in vitro. An IS rat model was established through middle cerebral artery occlusion (MCAO) surgery, and triphenyltetrazolium chloride (TTC) staining, behavioral scoring, Evans blue leakage, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining were performed to investigate the effects of COL on cerebral infarct size, neurological function, blood-brain barrier (BBB) and neuroinflammation in IS rats. An in vitro model of IS was established on hCMEC/D3 cells through oxygen-glucose deprivation/reperfusion (OGD/R), and cell counting kit-8 assay, reactive oxygen species (ROS) detection, scratch test and Transwell test were conducted to examine the influence of COL on cell viability, oxidative stress and migration ability. Lipidomics technology, real-time quantitative PCR and Western blot experiments were used to investigate the regulation and mechanism of COL on lipid metabolism in the brain of IS rats. All the animal experiments were approved by Ethical Committee of Animal Experiments of China Pharmaceutical University (No.2022-02-23). Our results showed that intragastric administration of COL could significantly reduce the area of cerebral infarction, improve neurological deficits, lower the levels of inflammatory factors, and protect against the blood-brain barrier damage of rats with IS. OGD/R modeling resulted in a significant decrease in the viability, an elevation in intracellular ROS levels, and a weakened cell migration ability of hCMEC/D3 cells. COL treatment could effectively protect hCMEC/D3 cells from damage caused by OGD/R. More importantly, cerebral ischemia led to significant lipid metabolism disorders in the brain of rats, and significant accumulation of intracerebral triglycerides (TAG) and ceramides (Cer) was observed in IS rats. COL was proved to significantly reverse lipid metabolism disorders in the brain of IS rats and reduce the content of cytotoxic lipid Cer by upregulating the intracerebral levels of an acid ceramidase called N-acylsphingosine amidehydrolase 1 (ASAH1). In summary, COL was proved to be a promising and effective candidate for IS treatment, which could alleviate cerebral ischemic injury by regulating abnormal lipid metabolism.

OBJECTIVE: To evaluate the diagnostic value of the expression levels of cytokines interleukin-6(IL-6), interleukin-10 (IL-10) and chemokine （C-X-C motif） ligand-13 (CXCL-13) in cerebrospinal fluid (CSF) for central nervous system infiltration of lymphoma. METHODS: Forty patients diagnosed as lymphoma or acute lymphoblastic leukemia in General Hospital of Northern Theater Command from July 2020 to July 2021 were collected and recorded their CSF indexes, including pressure, protein, Pandy test, nucleated cell count, glucose and chlorine content in CSF. The levels of cytokines IL-6, IL-10 and CXCL-13 were detected by Enzyme-linked immunosorbent assay. RESULTS: The patients were divided into CNSI (central nervous system infiltration) group and non-CNSI group, the average levels of IL-6, IL-10, CXCL-13 and IL-10/IL-6 ratio in CNSI group were higher than those in non-CNS group, but the difference of IL-10/IL-6 ratio between the two groups was statistically significant (P<0.05). Then the patients were divided into protein elevated(n=14) group and protein normal group(n=26), the levels of IL-6 ［ (5.78±2.69) pg/ ml］ and CXCL-13 ［(0.83±0.59) pg/ml］ in protein elevated group were significantly higher than those in the protein normal group ［IL-6: (2.41±1.16) pg/ml; CXCL-13: (0.38±0.18) pg/ml］ (P<0.05). Further analysis of the expression levels of the cytokines in non-CNSI group (n=32), IL-6, IL-10, CXCL-13 level and IL-10/IL-6 ratio in the protein elevated group (n=12) were higher than those in the protein normal group (n=20), but the difference was not statistically significant. CONCLUSION The levels of IL-6, IL-10 and CXCL-13 in CSF of lymphoma patients with CNS infiltration were higher than those in non-CNS infiltration group, and those in patients with protein elevated group are higher than those in the protein normal group.
Humans ; Central Nervous System ; Cytokines ; Interleukin-10 ; Interleukin-6 ; Lymphoma

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

The medicinal history of Pien Tze Huang is long, and it is the only "double top secret" variety of technology and formula at present. It has the effects of clearing heat and detoxifying, detumescence and pain, cooling blood and removing blood stasis. At present, researchers have analyzed and identified some compounds in Pien Tze Huang and its precious medicinal materials, such as Panax notoginseng, calculus bovis, snake gall and musk, and conducted activity screening, pharmacokinetics and pharmacological related studies on these chemical components. It was found that Pien Tze Huang had a significant effect on the treatment of acute and chronic hepatitis, ulcer, colon cancer, liver cancer and other diseases. The purpose of this paper is to systematically discuss the research achievements of researchers in recent years on the material basis, pharmacological effects and clinical application of Pien Tze Huang, with a view to providing ideas for the further research of Pien Tze Huang.

Aim To investigate the antibacterial activity and anti-resistant mutation ability of Qiguiyin decoction (a traditional Chinese herbal formula) combined with levofloxacin against pseudomonas aeruginosa byantibacterial experiment in vitro and serum pharmacology. Methods The minimal inhibitory concentrations (MICs) of levofloxacin and Qiguiyin decoction were detected respectively by the broth dilution technique.The MIC of the combination of two drugs was determined by the micro chessboard dilution method. The effects of combined drugs on enhancing the antibacterial activity of different strains were evaluated respectively by calculating the fractional inhibitory concentration index (FICI). The drug-containing serum of levofloxa-cin group, Qiguiyin decoction group, Qiguiyin decoction combined with levofloxacin group and control group was prepared. The antibacterial rate, MIC and MBC of 10% ~ 90% serum against the two strains were determined. Results Combined with Qiguiyin decoction, MIC of levofloxacin against pseudomonas aeruginosa (standard/resistant) decreased significantly, 0. 5 < FICI ^ 1. With the increase of the proportion of serum, the inhibitory rate of 10% ~ 90% drug-containing serum to pseudomonas aeruginosa (standard/resistant) increased gradually.compared with the control group, the inhibitory effect of the Qiguiyin group on bacteria was significantly enhanced. The MIC

OBJECTIVE: To investigate the factors related to renal impairment in patients with diabetic kidney disease (DKD) from the perspective of integrated Chinese and Western medicine. METHODS: Totally 492 patients with DKD in 8 Chinese hospitals from October 2017 to July 2019 were included. According to Kidney Disease Improving Global Outcomes (KDIGO) staging guidelines, patients were divided into a chronic kidney disease (CKD) 1-3 group and a CKD 4-5 group. Clinical data were collected, and logistic regression was used to analyze the factors related to different CKD stages in DKD patients. RESULTS: Demographically, male was a factor related to increased CKD staging in patients with DKD (OR=3.100, P=0.002). In clinical characteristics, course of diabetes >60 months (OR=3.562, P=0.010), anemia (OR=4.176, P<0.001), hyperuricemia (OR=3.352, P<0.001), massive albuminuria (OR=4.058, P=0.002), atherosclerosis (OR=2.153, P=0.007) and blood deficiency syndrome (OR=1.945, P=0.020) were factors related to increased CKD staging in patients with DKD. CONCLUSIONS Male, course of diabetes >60 months, anemia, hyperuricemia, massive proteinuria, atherosclerosis, and blood deficiency syndrome might indicate more severe degree of renal function damage in patients with DKD. (Registration No. NCT03865914).
Humans ; Male ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Hyperuricemia ; Kidney ; Proteinuria ; Renal Insufficiency, Chronic/complications*

OBJECTIVE: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients. METHODS: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup. RESULTS: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens. CONCLUSIONS There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern.
Humans ; Syndrome ; Ischemic Stroke ; Medicine, Chinese Traditional ; Liver ; Phenotype

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Mice ; Animals ; Transcriptome ; Aging/metabolism* ; Cochlea ; Stria Vascularis ; Presbycusis